| First Author | Carpio VH | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 7 | Pages | 101310 |
| PubMed ID | 32634740 | Mgi Jnum | J:336582 |
| Mgi Id | MGI:6717752 | Doi | 10.1016/j.isci.2020.101310 |
| Citation | Carpio VH, et al. (2020) T Helper Plasticity Is Orchestrated by STAT3, Bcl6, and Blimp-1 Balancing Pathology and Protection in Malaria. iScience 23(7):101310 |
| abstractText | Hybrid Th1/Tfh cells (IFN-gamma(+)IL-21(+)CXCR5(+)) predominate in response to several persistent infections. In Plasmodium chabaudi infection, IFN-gamma(+) T cells control parasitemia, whereas antibody and IL-21(+)Bcl6(+) T cells effect final clearance, suggesting an evolutionary driver for the hybrid population. We found that CD4-intrinsic Bcl6, Blimp-1, and STAT3 coordinately regulate expression of the Th1 master regulator T-bet, supporting plasticity of CD4 T cells. Bcl6 and Blimp-1 regulate CXCR5 levels, and T-bet, IL-27Ralpha, and STAT3 modulate cytokines in hybrid Th1/Tfh cells. Infected mice with STAT3 knockout (KO) T cells produced less antibody and more Th1-like IFN-gamma(+)IL-21(-)CXCR5(lo) effector and memory cells and were protected from re-infection. Conversely, T-bet KO mice had reduced Th1-bias upon re-infection and prolonged secondary parasitemia. Therefore, each feature of the CD4 T cell population phenotype is uniquely regulated in this persistent infection, and the cytokine profile of memory T cells can be modified to enhance the effectiveness of the secondary response. |
